國家衛生研究院 NHRI:Item 3990099045/3298

NHRI > Institute of Biotechnology and Pharmaceutical Research > John Tsu-An Hsu > Periodical Articles > Item 3990099045/3298

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3298

Title:	Amantadine as a regulator of internal ribosome entry site
Authors:	Chen, YJ;Zeng, SJ;Hsu, JT;Horng, JT;Yang, HM;Shih, SR;Chu, YT;Wu, TY
Contributors:	Division of Biotechnology and Pharmaceutical Research
Abstract:	Aim: Studies of eukaryotes have yielded 2 translation initiation mechanisms: a classical cap-dependent mechanism and a cap-independent mechanism proceeding through the internal ribosomal entry site (IRES). We hypothesized that it might be possible to identify compounds that may distinguish between cap-dependent translation and cap-independent IRES-mediated translation. Methods: To facilitate compound screening, we developed bicistronic reporter constructs containing a ?-galactosidase gene (?-gal) and a secreted human placental alkaline phosphatase (SEAP) reporter gene. Following transcription, the ?-gal gene is translated by a cap-dependent mechanism, while SEAP expression is controlled by the IRES derived from either enterovirus 71 (EV-71) or encephalomyocardi-tis virus (EMCV). This assay could potentially identify compounds that inhibit SEAP expression (cap-independent) without affecting ?-gal activity (cap-dependent). Results: Using a bicistronic plasmid-based transient transfection assay in the COS-1 cells, we identified amantadine, a compound that inhibited the IRES of EV71- and EMCV-mediated cap-independent translation but did not interfere with cap-dependent translation when the dose of amantadine was lower than 0.25 mg/mL. Conclusion: These results imply that amantadine may distinguish between cap-dependent translation and cap-independent IRES-mediated translation and can be used to regulate gene expression at a translational level. ?2008 CPS and SIMM.
Date:	2008-11
Relation:	Acta Pharmacologica Sinica. 2008 Nov;29(11):1327-1333.
Link to:	http://dx.doi.org/10.1111/j.1745-7254.2008.00876.x
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1671-4083&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000260527300007
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=55149088381
Appears in Collections:	[John Tsu-An Hsu] Periodical Articles

Files in This Item:

File	Description	Size	Format
SCP55149088381.pdf		625Kb	Adobe PDF	848	View/Open

Loading...